House flies, Musca domestica L. (Diptera: Muscidae), are major pests at animal production facilities. Insecticides, particularly pyrethroids, have been used for control of house fly populations for more than 30 yr, but the evolution of resistance will likely jeopardize fly control efforts. A major mechanism of pyrethroid resistance in the house fly is target site insensitivity (due to mutations in the Voltage-sensitive sodium channel [Vssc]). Based on a survey of house fly populations in 2007 and 2008, the most common resistance allele at 2/3 of the states in the United States is kdr-his. This was unexpected given the relatively lower level of resistance this allele confers, and led to speculation that the kdr-his allele may have a minimal fitness cost in the absence of insecticide. The goal of this study was to evaluate the fitness cost of kdr-his by monitoring the changes in allele frequency over 15 generations in the absence of insecticide. In crosses with two different insecticide susceptible strains, we found that kdr-his had a significant fitness cost. The implications of these results to insecticide resistance monitoring and management are discussed.